Hierarchical Particle Approach for Co-Precipitated Amorphous Solid Dispersions for Use in Preclinical In Vivo Studies

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Amorphous solid dispersions (ASDs) enhance drug solubility and bioavailability.
• Spray drying is a common method for ASD production but has limitations like processing challenges and batch variability.
• Co-precipitation offers an alternative route to ASDs with potential advantages.

Purpose of the Study:

• To develop a streamlined co-precipitation process for generating amorphous solid dispersions (ASDs) for early safety studies.
• To create composite particles incorporating co-precipitated amorphous dispersions (cPADs) for improved re-dispersibility.
• To compare the properties and performance of cPADs with spray-dried ASDs.

Main Methods:

• Utilized co-precipitation to generate amorphous solid dispersions (ASDs).
• Developed a hierarchical particle approach to create composite particles with water-soluble excipients.
• Evaluated stability, thermal properties, and in vivo pharmacokinetics of the cPADs.

Main Results:

• Achieved a rapid, safely contained co-precipitation process with high recovery yields.
• Generated composite particles demonstrating rapid re-dispersibility for uniform suspension.
• Demonstrated that cPADs exhibit comparable stability, thermal properties, and in vivo pharmacokinetics to spray-dried ASDs.

Conclusions:

• Co-precipitation is a viable and effective method for producing amorphous solid dispersions (ASDs) for pharmaceutical applications.
• The developed hierarchical particle approach enhances the utility of cPADs in safety studies.
• Co-precipitation presents a promising alternative to spray drying for ASD manufacturing, overcoming several limitations.